2017肝硬化门静脉高压出血风险分层、诊断和治疗指南

Risk Stratification

Guidance statements
Cirrhosis should be described, analyzed, and managed in two distinct clinical stages, compensated and decompensated, defined by thepresence or absence of overt clinical complications of cirrhosis (ascites, VH, and HE).
Patients with compensated cirrhosis should be substaged into those with mild PH and those with CSPH, an entity that predicts the development of more-advanced stages.
Patients with CSPH are substaged into those with and without GEV.
Treatment of PH differs depending on the stage and substages of cirrhosis, because prognosis and mechanisms of disease (and therefore therapeutic targets) are different.

Pathophysiological Bases of Therapy

Diagnosis and Monitoring

a) NONINVASIVE TESTS IN THE DIAGNOSIS OF CLINICALLY SIGNIFICANT PORTAL HYPERTENSION

Guidance statements
HVPG measurement is the gold-standard method to assess the presence of CSPH, defined asan HVPG>=10 mm Hg.
CSPH can be identified by noninvasive tests:LS > 20-25 kPa, alone or combined with platelet count and spleen size. The presence of portosystemic collaterals on imaging is sufficient to diagnose CSPH.
Patients with GEV on endoscopy have, by definition, CSPH.

b) NONINVASIVE TESTS IN THE DIAGNOSIS OF GASTROESOPHAGEAL VARICES

Guidance statements
Patients with an LS <20 kPa and platelet count >150,000/mm3 have a very low probability (<5%) of having high-risk varices, and EGD can be circumvented.
In patients who do not meet these criteria,screening endoscopy for the diagnosis of GEV is recommended when the diagnosis of cirrhosis is made.

c) MONITORING THE DEVELOPMENT OF CLINICALLY SIGNIFICANT PORTAL HYPERTENSION, VARICES, AND HIGH-RISK VARICES

d) MONITORING CHANGES IN HEPATIC VENOUS PRESSURE GRADIENT

Guidance statements
Patients with compensated cirrhosis (CC) without varices on screening endoscopy should have endoscopy repeated every 2 years (with ongoing liver injury or associated conditions,such as obesity and alcohol use) or every 3 years (if liver injury is quiescent, e.g., after viral elimination, alcohol abstinence).
Patients with CC with small varices on screening endoscopy should have endoscopy repeated every year (with ongoing liver injury) or every 2 years (if liver injury is quiescent, e.g., after viral elimination, alcohol abstinence).

Patients with CC without varices or with small varices who develop decompensation should have a repeat endoscopy when this occurs.
Monitoring changes in HVPG should not be performed routinely (outside clinical trials).
Noninvasive tests do not correlate well with changes in HVPG.

Management

a) PATIENTS WITH COMPENSATED CIRRHOSIS AND MILD PORTAL HYPERTENSION

Guidance statements
In patients in the earliest stage of compensated cirrhosis (patients with mild PH), the objective of treatment is to prevent development of CSPH/decompensation and perhaps even to achieve regression of cirrhosis.
Elimination of the etiologic agent is the current mainstay of therapy.

Drugs that act on portal flow, such as NSBBs,will be mostly ineffective in this substage, given that the hyperdynamic circulatory state is not fully developed.

b) PATIENTS WITH COMPENSATED CIRRHOSIS AND CLINICALLY SIGNIFICANT PORTAL HYPERTENSION, BUT WITHOUT GASTROESOPHAGEAL VARICES

Guidance statements
In patients with cirrhosis and CSPH but without varices, the objective of treatment should no longer be to prevent varices, but to prevent clinical decompensation.
There is no evidence at present to recommend theuse of NSBBs in preventing formation of varices.

c) PATIENTS WITH COMPENSATED CIRRHOSIS AND GASTROESOPHAGEAL VARICES

c.1. Prevention of First Variceal Hemorrhage in Patients With Medium/Large Esophageal Varices

Guidance statements
Either traditional NSBBs (propranolol, nadolol), carvedilol, or EVL is recommended for the prevention of first VH (primary prophylaxis) in patients with medium or large varices (Table 3 for doses and schedules).

Choice of treatment should be based on patient preference and characteristics.
Patients on NSBBs or carvedilol for primary prophylaxis do not require monitoring with serial EGD.
Combination therapy NSBB plus EVL is not recommended in this setting.
TIPS placement is not recommended in the prevention of first VH.

c.2. Prevention of First Variceal Hemorrhage in Patients With Small Esophageal Varices

Guidance statement
NSBB is the recommended therapy for patients with high-risk small EV (Table 3 for doses).

d) PATIENTS PRESENTING WITH ACUTE ESOPHAGEAL VARICEAL HEMORRHAGE

Guidance statements
PRBC transfusion should be done conservatively, starting to transfuse when the hemoglobin reaches a threshold of around 7g/dL with the goal of maintaining it between 7 and 9g/dL.
Short-term (maximum 7 days) antibiotic prophylaxis should be instituted in any patient with cirrhosis and GI hemorrhage.

Intravenous ceftriaxone 1 g/24 h is the antibiotic of choice and should be used for a maximum of 7 days (consider discontinuing when hemorrhage has resolved and vasoactive drugs
discontinued).
Vasoactive drugs (SMT or its analogue, octreotide; VP or its analogue, terlipressin) should be initiated as soon as VH is suspected (Table 4 for recommended doses and schedules).

EGD should be performed within 12 hours of admission and once the patient is hemodynamically stable.
If a variceal source is confirmed/suspected,EVL should be performed.
In patients at high risk of failure or rebleeding(CTP class C cirrhosis or CTP class B with active bleeding on endoscopy) who have no contraindications for TIPS, an “early” (preemptive) TIPS within 72 hours from EGD/EVL may benefit selected patients.
For patients in whom an early TIPS is not performed, intravenous vasoactive drugs should be continued for 2-5 days and NSBBs initiated once vasoactive drugs are discontinued. Rescue TIPS is indicated in these patients if hemorrhage cannot be controlled or if bleeding recurs despite vasoactive drugs+EVL.
In patients in whom TIPS is performed successfully, intravenous vasoactive drugs can be discontinued.

e) PATIENTS WHO HAVE RECOVERED FROM AN EPISODE OF ACUTE ESOPHAGEAL VARICEAL HEMORRHAGE

Guidance statements
Combination of NSBB+EVL is first-line therapy in the prevention of rebleeding (Table 5 for recommended doses and schedules).

Patients who have a TIPS placed successfully during the acute episode do not require NSBBs or EVL.
TIPS is the recommended rescue therapy in patients who experience recurrent hemorrhage despite combination therapy NSBB+EVL.

Gastric Varices

a) PREVENTION OF FIRST HEMORRHAGE FROM GASTRIC VARICES

Guidance statements
For prevention of first VH from GOV2 or IGV1, NSBBs can be used, although the data are not as strong as for EV.
Prevention of first bleeding from GOV1 varices may follow the recommendations for EV.
Neither TIPS nor BRTO are recommended to prevent first hemorrhage in patients with fundal varices that have not bled.

b) MANAGEMENT OF ACUTE HEMORRHAGE FROM GASTRIC VARICES

b.1. Endoscopic Therapy

b.2. Transjugular Intrahepatic Portosystemic Shunt

Guidance statements
Patients with acute bleeding from GV should be initially managed in a similar fashion to those bleeding from EV (using a restrictive transfusion policy, vasoactive drug infusion, and antibiotic prophylaxis).
In patients bleeding from GOV1 varices, either EVL (if technically feasible) or cyanoacrylate glue injection, if available, are the recommended endoscopic treatments.
TIPS is the treatment of choice in the control of bleeding from cardiofundal varices (GOV2 or IGV1).
Cyanoacrylate glue injection is an option for cases in which TIPS is not technically feasible, but it is not approved for treatment of GV in the United States and should be performed only in centers where the expertise is available.

c) PREVENTION OF REBLEEDING
c.1. Endoscopic Therapy and Nonselective Beta-Blockers

c.2. Transjugular Intrahepatic Portosystemic Shunt

c.3. Balloon Occluded Retrograde Transvenous Obliteration

Guidance statements
In patients who have recovered from a GOV1 hemorrhage, the combination of NSBBs and endoscopic variceal therapy (EVL or cyanoacrylate injection) is the first-line therapy to prevent rebleeding.
In patients who have recovered from GOV2 or IGV1 hemorrhage, TIPS or BRTO are first line treatments in the prevention of rebleeding.
Cyanoacrylate glue injection is an option for cases in which TIPS or BRTO are not technically feasible, but it is not approved for the treatment of GV in the United States and should be performed only in centers where the expertise is available.

Ectopic Varices

Guidance statement
The management of ectopic varices requires a thorough knowledge of the vascular supply to the varices and a multidisciplinary approach.
Options are ligation, cyanoacrylate injection, endosonographic coil placement, TIPS with or without embolization, and BRTO.

Special Populations

a) PATIENTS WITH REFRACTORY ASCITES OR AFTER SPONTANEOUS BACTERIAL PERITONITIS

Guidance statements
Refractory ascites and SBP are not absolute contraindications for treatment with NSBBs.In these patients, high doses of NSBBs (over 160 mg/day of propranolol or over 80 mg/day of nadolol) should be avoided, given that they might be associated with worse outcomes.

In patients with refractory ascites and severe circulatory dysfunction (systolic blood pressure < 90 mm Hg, serum sodium <130 meq/L, or HRS), the dose of NSBBs should be decreased or the drug temporarily held. NSBBs might be reintroduced if circulatory dysfunction improves.

b) PREVENTION OF REBLEEDING IN PATIENTS EXPERIENCING THE
FIRST VARICEAL HEMORRHAGE WHILE ON PRIMARY PROPHYLAXIS WITH NONSELECTIVE BETA-BLOCKERS OR ENDOSCOPIC VARICEAL LIGATION

Guidance statement
Patients failing primary prophylaxis for VH may be treated with the combination of NSBBs and EVL or, alternatively, with TIPS.Randomized trials are required in this group of patients to clarify the best therapeutic strategy.

c) PREVENTION AND TREATMENT OF VARICEAL HEMORRHAGE IN PATIENTS WITH HEPATOCELLULAR CARCINOMA

Guidance statement

Prevention and treatment of acute VH in patients with HCC should follow the same principles as those for patients without HCC.